Peptomers: A versatile approach for the preparation of diverse combinatorial peptidomimetic bead libraries
Novo Research Institute, Novo Alle, DK-2880 Bagsvaerd, Denmark
Research Center for Medical Biotechnology, Chemistry Department, Royal Veterinary and Agricultural University, Thorvaldsensvej 40, DK-1871 Frederiksberg C, Denmark
This report describes a versatile approach in the generation of peptidomimetic bead libraries. The method is based on the preparation of peptide-peptoid hybrids using the portioning-mixing procedure, which gives diverse peptidomimetic bead libraries composed of peptides, peptoids and peptide-peptoid hybrids. We term these peptomers, from peptide-peptoid hybrid polymers. The synthesis of the peptomers is easily accomplished by adapting the peptoid synthesis strategy, in which a primary amine reacts with bromoacetic acid, and we combine this methodology with conventional peptide synthesis. The sequence of the active compound is deduced by conventional microsequencing using Edman degradation chemistry, thus avoiding the synthesis of a coding structure or the addition of molecular tags. We demonstrate the utility of the peptomer approach by the synthesis of a bead library together with the identification of novel peptidomimetic ligands binding to the macromolecular targets streptavidin and the insulin receptor.
coding, combinatorial peptidomimetic library, dual color assay, Edman degradation, insulin receptor ligands, peptoid, streptavidin ligands
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